Browsing by Issue Date, starting with "2020-11-19"
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- Disruption of human meiotic telomere complex genes TERB1, TERB2 and MAJIN in men with non-obstructive azoospermiaPublication . Salas-Huetos, Albert; Tüttelmann, Frank; Wyrwoll, Margot J.; Kliesch, Sabine; Lopes, Alexandra M.; Gonçalves, João; Boyden, Steven E.; Wöste, Marius; Hotaling, James M.; GEMINI Consortium; Nagirnaja, Liina; Conrad, Donald F.; Carrell, Douglas T.; Aston, Kenneth I.Non-obstructive azoospermia (NOA), the lack of spermatozoa in semen due to impaired spermatogenesis affects nearly 1% of men. In about half of cases, an underlying cause for NOA cannot be identified. This study aimed to identify novel variants associated with idiopathic NOA. We identified a nonconsanguineous family in which multiple sons displayed the NOA phenotype. We performed whole-exome sequencing in three affected brothers with NOA, their two unaffected brothers and their father, and identified compound heterozygous frameshift variants (one novel and one extremely rare) in Telomere Repeat Binding Bouquet Formation Protein 2 (TERB2) that segregated perfectly with NOA. TERB2 interacts with TERB1 and Membrane Anchored Junction Protein (MAJIN) to form the tripartite meiotic telomere complex (MTC), which has been shown in mouse models to be necessary for the completion of meiosis and both male and female fertility. Given our novel findings of TERB2 variants in NOA men, along with the integral role of the three MTC proteins in spermatogenesis, we subsequently explored exome sequence data from 1495 NOA men to investigate the role of MTC gene variants in spermatogenic impairment. Remarkably, we identified two NOA patients with likely damaging rare homozygous stop and missense variants in TERB1 and one NOA patient with a rare homozygous missense variant in MAJIN. Available testis histology data from three of the NOA patients indicate germ cell maturation arrest, consistent with mouse phenotypes. These findings suggest that variants in MTC genes may be an important cause of NOA in both consanguineous and outbred populations.
- Prevalence of long-term disability in Portugal, 2014: Evidence of variation by personal and contextual factorsPublication . Santos, Joana; Torres, Ana Rita; Neto, Mariana; Namorado, SóniaBackground: Disability is not just a health problem. It is a wider phenomenon that reflects the gap between a person's capacities and their ability to fully perform the role demanded by society. Both personal and environmental factors are major contributors to disability. Objective: We aimed to estimate the prevalence of self-reported disability, overall and by sex, and associated factors in the Portuguese population in 2014. Methods: This was a cross sectional study based on data from the Portuguese National Health Interview Survey (2014) (n = 18,204). Long-term disability was evaluated based on the respondent reporting reasons for current disability lasting more than 6 months. Sex, age group, region, marital status, self-rated health, having or not health insurance, educational level, income, tobacco and alcohol consumption, physical activity and body mass index were considered as independent variables. A poisson model was performed to identify factors associated with disability. Results: Approximately 40% of the respondents reported having some long-term disability. Disability prevalence was higher in women than men (44.4% and 34.2%, respectively). Results showed age, region, education, self-rated health, physical activity and body mass index were associated with disability (p < 0.05). Conclusions: This study shows that along with personal factors, the context plays an important role in disability. We believe this piece of evidence emphasizes the factor context namely the region, when decision makers design disability related policies.
- Implementing an Influenza Vaccine Effectiveness Study in a Hospital Context in Portugal: The EVA Hospital ProjectPublication . Machado, Ausenda; Gomez, Verónica; Panarra, António; Poças, Jose; Corte-Real, Rita; Peres, Maria João; Nunes, Baltazar; EVA Hospital GroupIntroduction: The project ‘Integrated Monitoring of Vaccines in Europe’ aimed to measure seasonal influenza vaccine effectiveness against hospitalised adults, aged 65 years and over, with influenza. We describe the protocol implementation in Portugal. Material and Methods: We implemented a test-negative design, targeting community-dwelling patients aged 65 years old and over hospitalised with severe acute respiratory illness. Patients were reverse transverse-polymerase chain reaction tested for influenza. Cases were those positive for influenza while others were controls. Most variables were collected using hospital medical records. Selection bias was evaluated by comparison with the laboratory influenza test requests database according to demographic characteristics. Crude, season-adjusted influenza vaccine effectiveness was estimated as = 1 – odds ratio, and 95% confidence intervals were obtained by conditional logistical regression, matched with the disease onset month. Results: The recruitment rate was 37.8%. Most participants (n = 368) were female (55.8%) and aged 80 years old and over (55.8%). This was similar to values for potentially eligible severe acute respiratory illness patients (80 years old and over: 56.8%, female: 56.2%). The proportion of missing values was below 2.5% for 20 variables and above 5% (maximum 11.6%) for six variables. Influenza vaccine effectiveness estimates were 62.1% against AH1pdm09 (95% confidence intervals: -28.1 to 88.8), 14.9% against A(H3N2) (95% confidence intervals: -69.6 to 57.3), 43.6% against B/Yam (95% confidence intervals: -66.2 to 80.8). Discussion: Given the non-existence of a coded admission database in either participating hospital the selection of severe acute respiratory illness due to clinical features was the feasible one. These results are only valid for the older adult population residing in the catchment area of the two participating hospitals who were admitted to a public hospital with severe influenza or SARI symptoms. Conclusion: Despite the low participation rate, we observed comparable characteristics of participants and eligible severe acute respiratory illness patients. Data quality was high, and influenza vaccine effectiveness results were in accordance with the results of meta-analyses and European season-specific estimates. The final sample size was low, which inhibited obtaining estimates with good precision.
- Cytotoxic effects of single and binary mixtures of metal oxide nanoparticles and metal(loid) on A549 human cell line.Publication . Rosário, Fernanda; Bessa, Maria João; Brandão, Fátima; Costa, Carla; Lopes, Cláudia B.; Estrada, Ana Cristina; Tavares, Daniela S.; Teixeira, João Paulo; Reis, Ana TeresaBackground, Motivation and Objective: The need to assess the toxicity resulting from exposure to mixtures of chemicals has been recognized by the WHO and EU, as humans are simultaneously exposed to an array of natural and anthropogenic contaminants. Of particular interest are the potential combined effects resulting from interaction of nanoparticles (NPs) and metals. While the first are the current driving force for emerging contaminants, the latter, as legacy contaminants, remain a concern. Metals show strong affinity to NPs, which can change the uptake and toxicity to the organism of each individual contaminant. Studying the effects on the respiratory tract is of upmost relevance because of its constant contact with xenobiotics, resulting in adverse effects on the lung. Considering the above, the objective of this work was to assess and compare viability, cell cycle, and uptake of A549 cells after exposure to single and binary mixtures of titanium dioxide nanoparticles (TiO2NP), cerium oxide nanoparticles (CeO2NP), arsenic (As) and mercury (Hg). These chemicals were chosen because: 1) TiO2NP are among the most abundantly used NPs; 2) CeO2NP have been used in nanomedicine for its high biocompatibility and cytoprotective effect; and 3) As and Hg due to their non‐biodegradable, persistent, and extremely toxic character. This work intends to support adequate human risk assessment resulting from co-exposure to multiple contaminants.